唾液酸乳糖是母乳寡糖中的重要组成成分，对婴幼儿的健康成长具有十分重要的作用，在营养和医药行业具有广阔的应用前景。本项目拟在前期工作的基础上，利用合成生物学和系统代谢工程策略人工设计构建唾液酸乳糖合成途径并对合成体系进行适配优化。通过筛选唾液酸乳糖合成途径的生物元件，设计、组装生物合成代谢途径；构建菌株基因组尺度动态代谢网络，系统解析寡糖生物合成的关键代谢调控机制，鉴定产物合成的限速步骤和关键节点；采用基因编辑技术对菌株进行深层次基因组尺度网络编辑，实现菌株关键代谢途径的最优化适配，提高唾液酸乳糖生产效率。本项目能够揭示寡糖人工合成的关键代谢调控机制，为其优化合成体系提供理性指导，对于实现母乳寡糖的工业化应用具有重要意义。

As the most important component of human milk oligosaccharides (HMOs), sialyllactose plays a pivotal role in the healthy development of the breastfed infants, which displays the potential application in nutraceutical and pharmaceutical industry. In this project, we will employ synthetic biology and systems metabolic engineering strategies to design and construct the biosynthetic pathway of sialyllactose, and optimize the compatibility of designed systems. First, various biological parts will be optimized and assembled modularly. Subsequently, genome-scale dynamic metabolic network analysis will be used to elucidate the key metabolic and regulatory mechanisms of oligosaccharides synthesis; the potential targets influencing the production of oligosaccharides will be systematically identified, thus can supply rational strategies for engineering the strain. Finally, by using gene editing technology, the strain genome will be edited to meet the fitness of key metabolic pathway and to achieve the optimal production level. This project will not only reveal the pivotal metabolic and regulatory mechanisms of oligosaccharides high-efficient biosynthesis, but also provide a rational guidance for product enhancement. The results of this project will establish an important foundation for the production improvement of strain and further industrialization of HMOs.